Background and aims Liver stem cell therapy (SCT) is suggested as potential means to improve liver regeneration in advanced liver disease. However, data of randomized controlled trials are heterogeneous with no systematic histological evaluation. The aims of this study were firstly to specifically analyze the effect of autologous SCT on hepatic macrophages (implicated in liver regeneration) and second to perform an in depth transcriptome analysis in paired liver biopsies before and after transarterial administration of autologous hematopoietic stem cell in patients with alcoholic hepatitis. Methods Immunohistochemistry, in situ hybridization and global gene expression analysis were performed on liver biopsies of 58 patients (30 controls and 28 stem cell treated) both at baseline and after 4 weeks of follow-up. Results As reported in our initial report (Spahr et al., PlosOne 2013), patients who received SCT had a similar improvement of liver function over time as compared to controls and did not exhibit any increased proliferative activity in K7 positive liver progenitor cells nor in hepatocytes on the liver biopsy performed at 4 weeks. However, on repeat biopsy, patients who received SCT showed a more important CD68+ liver macrophagic expansion as compared to standard treatment (p<0.05). Transcriptome data revealed significant upregulated genes linked with inflammation (CD68, SAA, CXCL6), regeneration (SPINK1, HGF), fibrosis (COL1A) and stem cells (CD45). No major changes in gene pathways involved in liver growth, and in particular in cell cycle proteins were evidenced. SPINK1 mRNA identified as a good baseline prognostic factor (Lanthier et al., J Hepatol 2015) was present by in situ hybridization at week 4 in SCT patients in liver parenchyma areas adjacent to macrophage recruitment and liver cell proliferation. Conclusion The analysis of liver tissue after SCT demonstrated an expansion of macrophages concurrent with an upregulation in the expression of genes involved in inflammatory and regenerative pathways. With the negative clinical trial results, it has to be interpreted as a weak impact of SCT, which is not able to modify the clinical course of this severe disease.

Access type

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Accès libre

Publication date

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2017

Language

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Anglais

Conference

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"European Association for the Study of the Liver (ESAL) International congress", Amsterdam (du 19/04/2017 au 23/04/2017)